Introduction of a new synthetic route about 5-Bromoimidazo[1,2-a]pyridine-2-carbaldehyde

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,878197-68-3, its application will become more common.

Application of 878197-68-3 ,Some common heterocyclic compound, 878197-68-3, molecular formula is C8H5BrN2O, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.

Alternatively 5-(4-Methyl-1-piperazinyl)imidazo[1 ,2-a]pyridine-2-carbaldehyde can be prepared as follows: EPO A reactor is charged with 2-amino-6-bromopyridine (3.0 Kg1 17.3 mol) and dimethoxyethane ( 12 Liters) and stirred under nitrogen. 1 ,1 ,3-Trichloroacetone (5.6 Kg, 30.3 mol) is added to the 25 C solution in a single portion and the reaction solution is warmed to 65 0C jacket temperature and maintained for approximately 2 to 4 hours until judged complete. The reaction is cooled to 10 C and held for approximately one hour and filtered. The solids are rinsed with dimethoxyethane (6 Liters). The solid is placed back in the reactor and treated with dimethoxyethane (12 Liters) and 2N HCI (12 Liters) and warmed to aproximately 75 degrees for 16 to 20 hours or until judged complete. The reaction is cooled to approximately 1O0C and pH is adjusted to approximately 8 with 3 N NaOH. The resulting solids are filtered and washed with water. The solid is dried at 50 0C for 16 hours to yield 5-bromoimidazo[1 ,2-a]pyridine-2-carbaldehyde, (2.81 Kg, 72% yield) 1 H NMR (400 MHz, DMSO-D6) delta ppm 10.05 (s, 1 H) 8.66 (s, 1 H) 7.72 (s, 1 H) 7.42 (s, 1 H) 7.35 (s, 1 H). The reactor is charged with N-methylpiperazine (3.1 Kg, 31 mol ) and tetrahydrofuran (10 Liters) and stirred under nitrogen while cooling to negative 20 0C. n- Butyl lithium (10.4 L, 26.0 mol) is added to the reaction at a rate to maintain the negative 20 0C temp and the contents are stirred for 15 to 30 minutes. A slurry of 5- bromoimidazo[1 ,2-a]pyridine-2-carbaldehyde (2.79 Kg, 12.4 mol) in tetrahydrofuran (10 Liters) is added at a rate to maintain the reaction at ?0C. The slurry is washed in with additional tetrahydrofuran (6 Liters). The reaction is stirred for 30 minutes and warmed to approximately negative 10 0C. The reaction is quenched by addition of 6N HCI solution to achieve pH 4.0 while maintaining at ? 150C. The reaction is diluted with heptane (14 Liters) and the layers allowed to separate. The lower aqueous layer is drained and the upper organic layer is washed with 1 N HCI (2 x 1.5 Liters). The combined aqueous layers are stirred at 20 degrees and adjusted to pH 9 with 4N NaOH solution. The Aqueous layer is extracted with 10% iPrOH/CH2CI2 (3 x 28 Liters) and the combined organic layers are washed with saturated NaHCO3 solution (14 Liters) and evaporated at <25 0C to approximately 3 volumes, lsopropanol (28 Liters) is added and reaction again concentrated under reduced pressure to approximately 8.5 Liters, lsopropanol (17 Liters) is added and the reaction is treated with a solution of oxalic acid (1.0 Kg, 11.1 mol) in isopropanol (7 Liters) at a rate to maintain good stirring and temperature between approximately 25-4O0C. The reaction is stirred for 30 minutes and the solids are collected and washed with isopropanol (8.5 Liters) Solids are dried at 50 0C to yield 5-(4-methyl-1- piperazinyl)imidazo[1 ,2-a]pyridine-2-carbaldehyde, (2.25 Kg, 54% yield) 1 H NMR (400 MHz, DMSO-D6) delta ppm 10.01 (s, 1 H) 8.47 (s, 1 H) 7.41 (m, 2 H) 6.65 (m, 1 H) 3.34 (s, 8 H) 2.78 (s, 3 H) These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route,878197-68-3, its application will become more common. Reference:
Patent; SMITHKLINE BEECHAM CORPORATION; WO2006/76131; (2006); A2;,
Pyridine – Wikipedia,
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